Wound healing is the body's natural response for repairing and regenerating dermal and epidermal tissue. Wound healing is generally categorized into four stages: 1) clotting/hemostasis stage; 2) inflammatory stage; 3) tissue cell proliferation stage; and 4) tissue cell remodeling stage. The wound healing process is complex and fragile and may be susceptible to interruption or failure, especially in the instance of chronic wounds. A wound that does not heal in a predictable amount of time and in the orderly set of stages for typical wound healing may be categorized as chronic. For instance, wounds that do not heal within approximately one month from the point of inception are often categorized as chronic, and in some cases chronic wounds may never heal or may take years to do so. A number of factors may overwhelm the body's ability to effectively heal a wound, such as repeated trauma, continued pressure, an overriding illness, infection, or a restriction in blood supply to the wound area. More specifically, because the body's response to chronic wounds is often overwhelmed, the healing response goes awry, resulting in instability and disorganization in the healing process.
Chronic wounds may become caught in one or more of the four stages of wound healing, such as remaining in the inflammatory stage for too long, and thereby preventing the wound healing process to naturally progress. Similarly, a chronic wound may fail to adequately finish one stage of healing before moving on to the next, resulting in interference between the healing stages and potentially causing processes to repeat without an effective end. By way of further example, during the stage of epithelialization in typical wound healing, epithelial cells are formed at the edges of the wound or in proximity to a border or rim surrounding the wound bed and proliferate over the wound bed to cover it, continuing until the cells from various sides meet in the middle. Affected by various growth factors, the epithelial cells proliferate over the wound bed, engulfing and eliminating debris and pathogens found in the wound bed such as dead or necrotic tissue and bacterial matter that would otherwise obstruct their path and delay or prevent wound healing and closure. However, the epithelialization process in chronic wounds may be short-circuited or ineffective as the epithelial cells, needing living tissue to migrate across the wound bed, do not rapidly proliferate over the wound bed, or in some instances do not adequately respond at all during this particular stage of wound healing. As such, a need arises with chronic wounds to sterilize the wound site, as well as to establish communication between healthy tissue and wound tissue to promote epithelialization, fibroblast and epithelial migration, and neovascularization, and to bridge the gaps (i.e., including but not limited to structural and vascular gaps) between vital tissue surrounding the wound bed and tissue on the periphery of and within the wound bed itself.
Certain chronic wounds can be classified as ulcers of some type (i.e., diabetic ulcers, venous ulcers, and pressure ulcers). An ulcer is a break in a skin or a mucus membrane evident by a loss of surface tissue, tissue disintegration, necrosis of epithelial tissue, nerve damage and pus. Venous ulcers typically occur in the legs and are thought to be attributable to either chronic venous insufficiency or a combination of arterial and venous insufficiency, resulting in improper blood flow and/or a restriction in blood flow that causes tissue damage leading to the wound. Pressure ulcers typically occur in people with limited mobility or paralysis, where the condition of the person inhibits movement of body parts that are commonly subjected to pressure. Pressure ulcers, commonly referred to as “bed sores,” are caused by ischemia that occurs when the pressure on the tissue is greater than the blood pressure in the capillaries at the wound site, thus restricting blood flow into the area.
For patients with long-standing diabetes and with poor glycemic control, a common condition is a diabetic foot ulcer, symptoms of which include slow healing surface lesions with peripheral neuropathy (which inhibits the perception of pain), arterial insufficiency, damage to small blood vessels, poor vascularization, ischemia of surrounding tissue, deformities, cellulitis tissue formation, high rates of infection and inflammation. Cellulitis tissue includes callous and fibrotic tissue. Thus, due to the often concomitant loss of sensation in the wound area, diabetic patients may not initially notice small, non-lesioned wounds to legs and feet, and may therefore fail to prevent infection or repeated injury. If left untreated a diabetic foot ulcer can become infected and gangrenous which can result in disfiguring scars, foot deformity, and/or amputation.
As illustrated in FIGS. 1A-B, a diabetic foot ulcer may develop on any position of the foot, and typically occur on areas of the foot subjected to pressure or injury and common areas such as: on the dorsal portion of the toes; the pad of the foot; and the heel. Depending on its severity, the condition can vary in size, as illustrated in FIG. 1B, from a relatively small inflammation on the toe with cellulitis and unhealthy tissue, to a larger neuropathic lesion on the ball of the foot characterized by cellulitis and unhealthy tissue. If the ulcer is accompanied by osteomeylitis, deep abscess or critical ischema, the condition may trigger amputation.
Typically, ulcer treatment is dependant upon its location, size, depth, and appearance to determine whether it is neuropathic, ischemic, or neuro-ischemic. Depending on the diagnosis, antibiotics may be administered and if further treatment is necessary, the symptomatic area is treated more aggressively (e.g., by surgical debridement using a scalpel, scissors, or other instrument to cut necrotic and/or infected tissue from the wound, mechanical debridement using the removal of dressing adhered to the wound tissue, or chemical debridement using certain enzymes and other compounds to dissolve wound tissue) to remove unhealthy tissue and induce blood flow and to expose healthy underlying structure. Often, extensive post-debridement treatment such as dressings, foams, hydrocolloids, genetically engineered platelet-derived growth factor becaplermin and bio-engineered skins and the like may also be utilized.
Additionally, several other types of wounds may progress to a chronic, non-healing condition. For example, surgical wounds at the site of incision may progress inappropriately to a chronic wound or may progress to pathological scarring such as a keloid scar. Trauma wounds may similarly progress to chronic wound status due to infection or involvement of other factors within the wound bed that inhibit proper healing. Burn treatment and related skin grafting procedures may also be compromised due to improper wound healing response and the presence of chronic wound formation characteristics. In various types of burns, ulcers, and amputation wounds, skin grafting may be required. In certain instances, patients with ischemia or poor vascularity may experience difficulty in the graft “taking” resulting in the need for multiple costly skin grafting procedures. Finally, in patients where the risk of infection is high due to a weakened immune system (i.e., tissue impacted by radiation, patients undergoing cancer treatments, patients affected by immune compromised diseases such as HIV/AIDS), inflammation of a wound may be prolonged thereby interfering with the wound healing process and leading to wounds more susceptible to develop into chronic wounds, particularly where the wound site is unable to be sufficiently sterilized.
Various methods exist for treatment of chronic wounds, including antibiotic and antibacterial use, surgical or mechanical debridement, irrigation, topical chemical treatment, warming, oxygenation, and moist wound healing, which remain subject to several shortcomings in their efficacy. Accordingly, there remains a need for new and improved methods for use in the treatment of chronic wounds that address certain of the forgoing difficulties.